Currently, the resistance of tumor cells to chemotherapeutic treatment represents a huge problem subject to a continuous development. Drug resistance arises both in solid tumors and in lymphatic system tumors and can occur since the onset of a treatment or afterwards, after an initial positive response to the treatment. For instance, chemoresistance very often arises in the course of the treatment of tumor recurrences. An even more serious problem is represented by multiple chemoresistance, i.e. the occurrence, after a treatment with a given chemotherapeutic agent, to other chemotherapeutics.
The most reliable hypotheses about the origin of chemoresistance, which arises in most tumors initially responding to chemotherapeutic treatment, suggest that drug resistance results from a series of tumor cell mutation, from the ability of tumor cells to “learn” how to metabolize chemotherapeutics, to repair chemotherapeutic-induced damage in DNA, and to prevent chemotherapeutic-induced apoptosis.
An approach aiming at overcoming the problem of chemoresistance is the combination therapy with different types of chemotherapeutics: however, also in this case the outcomes are not satisfactory and lead to an alarmingly, increasingly frequent multiple resistance to various chemotherapeutics.
Despite the continuous research and development of new drugs, to be used also in combination, the problem of chemoresistance remains and seems to be unavoidable due to the malleable nature of cancer cells [Fojo T. and Bates S., Cancer Discov; 3(1); 20-3, 2012].
Therefore, there is a very strong need to overcome this problem.
Rutin, whose chemical name is 2-(3,4-dihydroxyphenyl)-4.5-dihydroxy-3-{3,4,5-trihydroxy-6-[(3,4,5-trihydroxy-6-methyloxan-2-yl)oxymethyl}oxan-2-yl]oxy-cromen-7-one, is a flavonoid glycoside consisting of aglycone quercetin (a flavonol) linked to disaccharide rutinose.

Rutin naturally occurs in many vegetables, in particular in the plants of the genus Citrus (citrus fruits) and Rheum (rhubarb), in buckwheat, in red wine, in asparagus, in peppermint, in eucalyptus, in many berries such as cranberry (Vaccinium macrocarpon), and mulberry.
The reinforcing effect of rutin on capillary walls and more generally its beneficial action on microcirculation are exploited in the treatment of hemorrhoids and hematomas.
Recent studies have pointed out the pharmacological properties of rutin, in particular its antiaggregating activity on platelets [Navarro-Núñez et al. (2008); J. Agric. Food Chem. 56 (9): 2970-6]; its anti-inflammatory activity [Guardia et al. (2001); Il Farmaco 56 (9): 683-7; Chan Hun Jung et al. (2007); Arch. Pharmacal Research 30 (12): 1599-1607]; and its anti-oxidant activity [Metodiewa et al. (1997); IUBMB Life 41 (5); 1067].
In-vitro studies have shown that rutin is able to inhibit the vascular endothelial growth factor, thus acting as an inhibitor of angiogenesis [Luo et al. (2008); Nutrition and Cancer 60 (6); 800-9].
Recently, Boutogaa et al. [Leukemia Research 35(2011) 1093-1101] have described how an extract of Hammada scoparia, containing rutin, is able to induce apoptosis in adhering leukemia cells. EP 2 119 434 describes the use of rutin in the treatment of acute myeloid leukemia, for preventing neoplastic recurrence and/or for preventing the occurrence of solid metastases. There is no mention of the effects of rutin on chemotherapeutic-resistant tumor cells.
WO 200178783 describes anti-tumor compositions comprising quercetin and many extracts of medicinal plants, but no mention is made on the activity towards chemoresistant cells.